Skip to main content
SpringerLink
Log in

Prospective randomized trial comparing efficacy of letrozole step-up protocol with letrozole plus gonadotropins for controlled ovarian stimulation and intrauterine insemination in patients with unexplained infertility

  • Gynecologic Endocrinology and Reproductive Medicine
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Purpose

Empirical treatment options for unexplained infertility treatment include controlled ovarian stimulation (COS) with clomiphene citrate, letrozole or gonadotropins followed by intrauterine insemination (IUI). Achieving consistent multifollicular development with letrozole generally requires addition of gonadotropins. However, the cost and discomfort of injections remains a drawback of this regimen. Therefore, there is a need for evolving newer cost-effective regimens for COS/IUI using orally administered drugs like letrozole.

Methods

Sixty couples with unexplained infertility (on standard infertility investigations) visiting the infertility clinic at a tertiary centre in North India were randomized into two groups. Group A COS was done by step-up protocol of letrozole from day 2 or 3 of menstrual cycle, starting with 2.5 mg and increased by 2.5 mg per day for next 3 days (2.5 mg, 5 mg, 7.5 mg, 10 mg). Group B COS was done with combination of letrozole and hMG (human menopausal gonadotropin). Starting from day 2 or 3 of menses, tablet letrozole 2.5 mg twice a day was given for 5 days. Intramuscular injection of hMG 150 IU was given every alternate day starting from day 7 and titrated according to the response. HCG was given when leading follicle was 17 mm and IUI done 36 h after HCG.

Results

Twenty-eight couples in letrozole step-up group (group A) and 30 couples in letrozole plus hMG group (group B), completed follow up for 44 and 55 cycles, respectively. Mean numbers of follicle ≥ 16 mm in both groups were comparable: 1.74 (± 0.83) in group A and 1.94 (± 0.68) in group B (p = 0.178). Ovulation rate of 90.9% (40/44) was achieved in group A, whereas it was 100% (55/55) in group B (p = 0.022), although there was no significant difference in clinical pregnancy rate per patient, which was 3/28 (10.7%) in group A versus 5/30 (16.67%) in group B (p = 0.707). The mean (SD) cost of medicines was significantly lower in group A Rs. 345.00 (00) compared to group B Rs. 2148.64 (515.67) [p < 0.0001]. There was one case each of hyperstimulation and multiple pregnancies in group B, while none in group A.

Conclusion

It is possible to achieve multifollicular development with use of novel letrozole step-up protocol, even without addition of gonadotropins, at significantly lower cost.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Practice Committee of the American Society for Reproductive Medicine (2006) Effectiveness and treatment for unexplained infertility. Fertil Steril 86:111–114

    Google Scholar 

  2. Gunn DD, Bates GW (2016) Evidence-based approach to unexplained infertility: a systematic review. Fertil Steril 105:1566–1574

    Article  Google Scholar 

  3. Crosignani PG, Walters DE, Soliani A (1991) The ESHRE multicentre trial on the treatment of unexplained infertility: a preliminary report. European Society of Human Reproduction and Embryology. Hum Reprod 6:953–958

    Article  CAS  Google Scholar 

  4. Casper RF, Mitwally MF (2012) A historical perspective of aromatase inhibitors for ovulation induction. Fertil Steril 98:1352–1355

    Article  CAS  Google Scholar 

  5. Healey S, Tan SL, Tulandi T, Biljan MM (2003) Effects of letrozole on superovulation with gonadotropins in women undergoing intrauterine insemination. Fertil Steril 80:1325–1329

    Article  Google Scholar 

  6. Fouda UM, Sayed AM (2011) Extended letrozole regimen versus clomiphene citrate for superovulation in patients with unexplained infertility undergoing intrauterine insemination: a randomized controlled trial. Reprod Biol Endocrinol 9:84

    Article  CAS  Google Scholar 

  7. Mitwally MF, Said T, Galal A, Chan S, Cohen M, Casper RF, Magarelli PC (2008) Letrozole step-up protocol: a successful superovulation. https://doi.org/10.1016/j.fertnstert.2008.02.071

    Article  Google Scholar 

  8. World Health Organization (2010) WHO laboratory manual for the examination and processing of human semen, 5th edn. World Health Organization, Geneva, p 271

    Google Scholar 

  9. Ager J, Huang H, Hansen KR, Baker V (2015) Letrozole, gonadotropin, or clomiphene for unexplained infertility. N Engl J Med 373:1230–1240

    Article  CAS  Google Scholar 

  10. Bedaiwy MA, Forman R, Mousa NA (2006) Cost- effectiveness of aromatase inhibitor co-treatment for controlled ovarian stimulation. Hum Reprod 21:2838–2844

    Article  Google Scholar 

  11. Pourali L, Ayati S, Tavakolizadeh S, Soleimani H, Sani FT (2017) Clomiphene citrate versus letrozole with gonadotropins in intrauterine insemination cycles: a randomized trial. Int J Reprod BioMed 15:49

    Article  Google Scholar 

  12. Shahrokh Tehrani Nejad E, Abediasl Z, Rashidi BH, Azimi Nekoo E, Shariat M, Amirchaghmaghi E (2008) Comparison of the efficacy of the aromatase inhibitor letrozole and clomiphene citrate gonadotropins in controlled ovarian hyperstimulation: a prospective, simply randomized, clinical trial. J Assist Reprod Genet 25:187–190

    Article  Google Scholar 

  13. Galal AF (2015) Letrozole step-up protocol: the effect of a novel superovulation induction protocol to enhance pregnancy rate in a couple with unexplained infertility undergoing intrauterine insemination. Fertil Steril 104:e328 (poseidon)

    Article  Google Scholar 

  14. Muhamad W (2016) The relationship between duration of infertility and intrauterine insemination: a multi-centers study. Dev Biol 1:3

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Nehru Hospital, Postgraduate Institute of Medical Education and Research (PGIMER), 3rd Floor, Chandigarh, India

    Japleen Kaur, Vanita Suri, Shalini Gainder & Aashima Arora

Authors
  1. Japleen Kaur
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vanita Suri
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shalini Gainder
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Aashima Arora
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

JK: protocol development, data collection, data analysis, manuscript writing. VS: protocol development, data collection, manuscript proofreading. SG: review of literature, Manuscript proofreading, and editing. AA: review of literature, manuscript proofreading, and editing.

Corresponding author

Correspondence to Aashima Arora.

Ethics declarations

Conflict of interest

All authors declare that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kaur, J., Suri, V., Gainder, S. et al. Prospective randomized trial comparing efficacy of letrozole step-up protocol with letrozole plus gonadotropins for controlled ovarian stimulation and intrauterine insemination in patients with unexplained infertility. Arch Gynecol Obstet 300, 1767–1771 (2019). https://doi.org/10.1007/s00404-019-05326-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00404-019-05326-2

Keywords

Search

Navigation